Automatic analyzers are used extensively to analyze the quantity of an ingredient in a sample, the analyzers applying light from a light source to the sample or to a reaction mixture that mixes the sample with a reagent, measuring the volume of resulting transmitted light of a single or multiple wavelengths, and calculating absorbance accordingly to determine the quantity of the ingredient. The quantity of the ingredient is calculated in accordance with the Lambert-Beer law.
With the above type of automatic analyzer, numerous reaction cells holding the reaction mixture are arranged circumferentially on a reaction disk that rotates and stops repeatedly. While the reaction disk is being rotated, a prearranged transmitted light measurement unit measures chronological changes in the absorbance at predetermined time intervals for about 10 minutes. Upon completion of the measurement, the reaction cells are washed by a washing mechanism before being used for another analysis.
Two major kinds of analyses are employed: color reactions involving substrates and enzymes, and agglutination reactions involving antigens and antibodies. The former kind of analyses represents biochemical analyses of which the test items include LDH (lactate dehydrogenase), ALP (alkaline phosphatase), and AST (aspartate aminotransferase). The latter kind of analyses denotes immunoassays of which the test items include CRP (C-reactive protein), IgG (immunoglobulin), and RF (rheumatoid factor).
A highly sensitive detection system is required for the above-mentioned immunoassays because the substances to be measured thereby have low blood concentrations. For example, consider the case where a reagent of latex particles whose surface is sensitized (bonded) with antibodies is used in an antigen-antibody reaction with antigens contained in a sample so as to bring about the agglutination of latex aggregates. In this case, light is applied to the reaction mixture, and the quantity of transmitted light (i.e., light not scattered by the latex aggregates) is measured to determine the quantity of an ingredient in the sample by what is known as the latex coagulating method for highly sensitive measurement.
Further, attempts have been made with automatic analyzers to measure the quantity of not transmitted light but scattered light from the sample for highly sensitive measurement.
Meanwhile, with the above-described automatic analyzers, there have been cases where the light from the light source is partially blocked or scattered by the presence of foreign matter or bubbles inside the reaction cells or within a fluid in a thermostatic bath outside the reaction cells, causing abnormalities in the reaction process that determines the quantity of the target substance.
The abnormalities induced by foreign matter or by bubbles in the reaction process may be of three types: (1) a sudden fluctuation at a single point of measurement, (2) sudden fluctuations at multiple points of measurement, and (3) gradual fluctuations throughout the entire reaction process. The abnormality of type (1) above in the reaction process occurs because the foreign matter or bubbles within the fluid inside the thermostatic oven outside the reaction cells traverse the optical axis for photometry, causing a temporary drop in the quantity of transmitted light (rise in absorbance) or a temporary rise in the quantity of scattered light.
The abnormality of type (2) above in the reaction process takes place because the foreign matter or bubbles floating in the reaction mixture in the reaction cells traverse over time the optical axis for photometry, triggering drops in the quantity of transmitted light or rises in the quantity of scattered light at multiple points of measurement.
The abnormality of type (3) above in the reaction process occurs because very small bubbles stuck on the inner wall surface of the reaction cells gradually grow or migrate within a reaction time, causing the measuring luminous flux to be partially blocked or scattered and bringing about a gradual decrease in the quantity of light (gradual increase in absorbance) or a gradual increase in the quantity of scattered light from an apparent reaction taking place.
The above abnormalities in the reaction process are known to affect the correctness or the accuracy of the results of measurement, and constitute a major impediment to bringing about highly sensitive measurement.
The abnormalities of types (1) and (2) in the reaction process can be checked by techniques described in Patent Document 1 for comparing rates of changes in the reaction process or by techniques disclosed in Patent Document 2 for calculating the Mahalanobis distance regarding normal reactions so as to distinguish abnormal reactions.
The abnormality of type (3) above in the reaction process is not easy to check during ordinary inspection work where the concentration of the target substance is unknown, because the reaction process is apparently normal.
Given the circumstances, Patent Document 3 discloses techniques involving an image acquisition unit for directly imaging the reaction cells in addition to the measurement unit for measuring the absorbance of the reaction mixture, whereby the reaction process and image information are used to check reaction process abnormalities caused by bubbles or the like.